A novel export pathway

杨柳

The lectin galectin-1 is exported from cells via a poorly characterized secretory pathway. On page 373, Seelenmeyer et al. demonstrate that the cell surface receptors to which the lectin binds on the exterior of the cell are also required for export of the glycoprotein from the interior.2 X: w* ]/ |$ C' l7 a1 ]1 r
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Galectin-1 interacts with ?-galactoside–containing sugar moieties on extracellular matrix and cell surface receptors. Based on previous work, researchers think galectin-1 is translated and folded in the cytoplasm before localizing to the inside of the plasma membrane and being exported.
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Seelenmeyer et al. found that galectin-1 mutants deficient for binding to ?-galactoside get stuck in the cytoplasm and are not exported. Moreover, cells that cannot produce the cell surface receptors that bind galectin-1 failed to export wild-type galectin-1. The fungal lectin CGL2, which resembles galectin-1 in its folded shape, was also trapped in the cytoplasm in these mutant cells, though wild-type cells exported it efficiently.( J$ B; Q3 i! r: U6 A

  u* V' d9 f0 U8 Q+ mSo how is a cell surface receptor working to export a protein from the cytoplasm? The researchers currently have two hypotheses. The receptor could act as a sink, skewing the intracellular–extracellular equilibrium in favor of the extracellular space. In a variant of this model, receptors may reach through a protein-conducting channel to contact the lectin and pull it through the membrane. Alternatively, some ?-galactoside–containing glycolipids may be flipped from their normal extracellular orientation to pick up intracellular galectin-1 before being flipped back again.Galectin-1 and CGL2 may not be the only proteins using a receptor-based export system. Another prime candidate is FGF2. It is a lectin that binds heparan sulfate moieties on proteoglycans and, like galectin-1, it appears to be completely folded before export.(Galectin gets exported thanks to its ext)